chr6-31949763-T-C

Variant names:

• chr6-31949763-T-C
• rs4151657
• NM_001710.6:c.1408+206T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001710.6(CFB):​c.1408+206T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 722,146 control chromosomes in the GnomAD database, including 42,360 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.27 (6791 hom., cov: 32)
  • Exomes 𝑓: 0.34 (35569 hom.)
• Consequence: CFB NM_001710.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.680
• Publications: 86 publications found

Genes affected

CFB (HGNC:1037): (complement factor B) This gene encodes complement factor B, a component of the alternative pathway of complement activation. Factor B circulates in the blood as a single chain polypeptide. Upon activation of the alternative pathway, it is cleaved by complement factor D yielding the noncatalytic chain Ba and the catalytic subunit Bb. The active subunit Bb is a serine protease which associates with C3b to form the alternative pathway C3 convertase. Bb is involved in the proliferation of preactivated B lymphocytes, while Ba inhibits their proliferation. This gene localizes to the major histocompatibility complex (MHC) class III region on chromosome 6. This cluster includes several genes involved in regulation of the immune reaction. Polymorphisms in this gene are associated with a reduced risk of age-related macular degeneration. The polyadenylation site of this gene is 421 bp from the 5' end of the gene for complement component 2. [provided by RefSeq, Jul 2008]

CFB Gene-Disease associations (from GenCC):

• atypical hemolytic-uremic syndrome with B factor anomaly

  Inheritance: Unknown, AD Classification: STRONG, MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, ClinGen
• complement factor b deficiency

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000244255 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 6-31949763-T-C is Benign according to our data. Variant chr6-31949763-T-C is described in ClinVar as Benign. ClinVar VariationId is 1259216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.338 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFB	NM_001710.6	c.1408+206T>C		intron_variant	Intron 10 of 17	ENST00000425368.7	NP_001701.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFB	ENST00000425368.7	c.1408+206T>C		intron_variant	Intron 10 of 17	1	NM_001710.6	ENSP00000416561.2
ENSG00000244255	ENST00000456570.5	c.2914+206T>C		intron_variant	Intron 22 of 29	2		ENSP00000410815.1

Frequencies

GnomAD3 genomes AF: 0.274 AC: 41185 AN: 150326 Hom.: 6792 Cov.: 32

Gnomad AFR AF: 0.0816

Gnomad AMI AF: 0.436

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.531

Gnomad EAS AF: 0.310

Gnomad SAS AF: 0.309

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.449

Gnomad NFE AF: 0.341

Gnomad OTH AF: 0.288

GnomAD4 exome AF: 0.344 AC: 196586 AN: 571696 Hom.: 35569 Cov.: 7 AF XY: 0.346 AC XY: 104317 AN XY: 301402

African (AFR) AF: 0.0774 AC: 1154 AN: 14908

American (AMR) AF: 0.384 AC: 9385 AN: 24458

Ashkenazi Jewish (ASJ) AF: 0.527 AC: 8434 AN: 15992

East Asian (EAS) AF: 0.376 AC: 12070 AN: 32110

South Asian (SAS) AF: 0.313 AC: 15772 AN: 50398

European-Finnish (FIN) AF: 0.352 AC: 10677 AN: 30324

Middle Eastern (MID) AF: 0.475 AC: 1141 AN: 2402

European-Non Finnish (NFE) AF: 0.346 AC: 128068 AN: 370648

Other (OTH) AF: 0.325 AC: 9885 AN: 30456

GnomAD4 genome AF: 0.274 AC: 41184 AN: 150450 Hom.: 6791 Cov.: 32 AF XY: 0.277 AC XY: 20333 AN XY: 73530

African (AFR) AF: 0.0814 AC: 3296 AN: 40476

American (AMR) AF: 0.325 AC: 4925 AN: 15154

Ashkenazi Jewish (ASJ) AF: 0.531 AC: 1843 AN: 3468

East Asian (EAS) AF: 0.310 AC: 1586 AN: 5120

South Asian (SAS) AF: 0.309 AC: 1461 AN: 4730

European-Finnish (FIN) AF: 0.365 AC: 3840 AN: 10534

Middle Eastern (MID) AF: 0.446 AC: 131 AN: 294

European-Non Finnish (NFE) AF: 0.341 AC: 23107 AN: 67684

Other (OTH) AF: 0.288 AC: 602 AN: 2088

Alfa AF: 0.333 Hom.: 38177

Bravo AF: 0.261

Asia WGS AF: 0.256 AC: 894 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 18, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	0.15
DANN	Benign	0.64
PhyloP100		-0.68
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4151657; hg19: chr6-31917540;